The goal of these experiments is to characterize the reactions which constitute the contact phase of intrinsic clotting. They are designed to establish and define at the molecular level the intermediate reactions which take place in purified systems and in plasma between contact activators and factor XI, factor XII, high molecular weight kininogen (contact activation cofactor, Fitzgerald factor), and prekallikrein (Fletcher factor), which lead to the formation of activated factor XI. For these experiments highly purified clotting factors are prepared and radiolabelled with 125I. The reaction of contact activators and different combinations of purified reactants in isolated systems will be evaluated and compared to reaction mechanisms and products generated in plasma.